This research proposes the continuation of a thorough and systematic microrheological study of the flow patterns and distributions of fluid velocity and shear rate in various regions of disturbed flow in the human and dog cardio- and cerebrovascular systems. This will be achieved through direct observation and film of the behavior of blood cells and model particles flowing in isolated transparent natural vessels prepared from dogs and dumans postmortem by the method recently developed by the applicant. Specific aims of the proposed research are: (1) to obtain precise and detailed flow patterns in regions of disturbed flow in the human and canine circulation under normal (physiological) and altered flow conditions; (2) to acquire information on the distributions of fluid velocity and shear rate existing in the regions of disturbed flow in order to identify the regions of high and low shear; and (3) to correlate the results with the incidence of vascular diseases in vivo. Long term objectives of the proposed research are: (1) to arrive at a better understanding of fluid dynamics of the mammalian circulation under normal (physiological) and altered flow conditions; and (2) to clarify the possible connection between flow and the localization of thrombosis and atherosclerosis. Plans for the next three years are to continue and complete the present studies on flow patterns in the dog aorta and the human Circle of Willis. In the dog aorta, flow experiments will be carried out in pulsatile flow to see if there is any major difference in the flow characteristics between steady and pulsatile flow. Studies will then be extended to the human coronary circulation and descending aorta to obtain detailed flow patters at the primary and secondary branching sites of the left and right coronary arteries and at the aorto-renal artery junctions. In the human Circle of Willis, studies will be focused first on flow patterns at the junctions where the internal carotid artery meets the middle cerebral, posterior communicating and anterior cerebral arteries, then on the distributions of blood flow to each artery of the Circle of Willis under normal (physiological) and altered flow conditions.